Publications by authors named "Kristina Gemzell-Danielsson"

239 Publications

Stromal Heterogeneity in the Human Proliferative Endometrium-A Single-Cell RNA Sequencing Study.

J Pers Med 2021 May 22;11(6). Epub 2021 May 22.

Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet, and Karolinska University Hospital, S-171 64 Solna, Sweden.

The endometrium undergoes regular regeneration and stromal proliferation as part of the normal menstrual cycle. To better understand cellular interactions driving the mechanisms in endometrial regeneration we employed single-cell RNA sequencing. Endometrial biopsies were obtained during the proliferative phase of the menstrual cycle from healthy fertile women and processed to single-cell suspensions which were submitted for sequencing. In addition to known endometrial cell types, bioinformatic analysis revealed multiple stromal populations suggestive of specific stromal niches with the ability to control inflammation and extracellular matrix composition. Ten different stromal cells and two pericyte subsets were identified. Applying different R packages (Seurat, SingleR, Velocyto) we established cell cluster diversity and cell lineage/trajectory, while using external data to validate our findings. By understanding healthy regeneration in the described stromal compartments, we aim to identify points of further investigation and possible targets for novel therapy development for benign gynecological disorders affecting endometrial regeneration and proliferation such as endometriosis and Asherman's syndrome.
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http://dx.doi.org/10.3390/jpm11060448DOI Listing
May 2021

Single-cell RNA sequencing of cultured human endometrial CD140bCD146 perivascular cells highlights the importance of in vivo microenvironment.

Stem Cell Res Ther 2021 May 29;12(1):306. Epub 2021 May 29.

Shenzhen Key Laboratory of Fertility Regulation, Reproductive Medicine Center, The University of Hong Kong - Shenzhen Hospital, Shenzhen, China.

Background: Endometrial mesenchymal-like stromal/stem cells (eMSCs) have been proposed as adult stem cells contributing to endometrial regeneration. One set of perivascular markers (CD140b&CD146) has been widely used to enrich eMSCs. Although eMSCs are easily accessible for regenerative medicine and have long been studied, their cellular heterogeneity, relationship to primary counterpart, remains largely unclear.

Methods: In this study, we applied 10X genomics single-cell RNA sequencing (scRNA-seq) to cultured human CD140bCD146 endometrial perivascular cells (ePCs) from menstrual and secretory endometrium. We also analyzed publicly available scRNA-seq data of primary endometrium and performed transcriptome comparison between cultured ePCs and primary ePCs at single-cell level.

Results: Transcriptomic expression-based clustering revealed limited heterogeneity within cultured menstrual and secretory ePCs. A main subpopulation and a small stress-induced subpopulation were identified in secretory and menstrual ePCs. Cell identity analysis demonstrated the similar cellular composition in secretory and menstrual ePCs. Marker gene expression analysis showed that the main subpopulations identified from cultured secretory and menstrual ePCs simultaneously expressed genes marking mesenchymal stem cell (MSC), perivascular cell, smooth muscle cell, and stromal fibroblast. GO enrichment analysis revealed that genes upregulated in the main subpopulation enriched in actin filament organization, cellular division, etc., while genes upregulated in the small subpopulation enriched in extracellular matrix disassembly, stress response, etc. By comparing subpopulations of cultured ePCs to the publicly available primary endometrial cells, it was found that the main subpopulation identified from cultured ePCs was culture-unique which was unlike primary ePCs or primary endometrial stromal fibroblast cells.

Conclusion: In summary, these data for the first time provides a single-cell atlas of the cultured human CD140bCD146 ePCs. The identification of culture-unique relatively homogenous cell population of CD140bCD146 ePCs underscores the importance of in vivo microenvironment in maintaining cellular identity.
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http://dx.doi.org/10.1186/s13287-021-02354-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164319PMC
May 2021

Persistent organic pollutants and the size of ovarian reserve in reproductive-aged women.

Environ Int 2021 May 1;155:106589. Epub 2021 May 1.

Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet and Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden. Electronic address:

Industrial chemicals such as persistent organic pollutants (POPs) have been associated with reduced fertility in women, including longer time-to-pregnancy (TTP), higher odds for infertility, and earlier reproductive senescence. Fertility is highly dependent on the ovarian reserve, which is composed of a prenatally determined stock of non-growing follicles. The quantity and quality of the follicles decline with age, thereby eventually leading to menopause. In the clinical setting, assessing ovarian reserve directly through the histological analysis of follicular density in ovaries is not practical. Therefore, surrogate markers of ovarian reserve, such as serum anti-Müllerian hormone (AMH) are typically used. Here, we studied associations between chemical exposure and ovarian reserve in a cohort of pregnant women undergoing elective caesarean section (n = 145) in Stockholm, Sweden. Full data (histological, clinical, serum) were available for 50 women. We estimated the size of the reserve both directly by determining the density of follicles in ovarian cortical tissue samples, and indirectly by measuring AMH in associated serum samples. Concentrations of 9 organochlorine pesticides (OCPs), 10 polychlorinated biphenyls (PCBs), 3 polybrominated diphenylethers (PBDEs) and 9 perfluoroalkyl substances (PFAS) were determined in serum, and clinical data were retrieved from electronic medical records. Healthy follicle densities (median 0, range 0-193 follicles/mm) and AMH levels (median 2.33 ng/mL, range 0.1-14.8 ng/mL) varied substantially. AMH correlated with the density of growing follicles. Twenty-three chemicals detected in more than half of the samples were included in the analyses. None of the chemicals, alone or as a mixture, correlated with AMH, growing or atretic follicles. However, HCB, transnonachlor, PCBs 74 and 99 were associated with decreased non-growing follicle densities. HCB and transnonachlor were also negatively associated with healthy follicle density. Further, mixture of lipophilic POPs (PBDE 99, p,p'-DDE, and PCB 187) was associated with lower non-growing follicle densities. In addition, exposure to HCB, p,p'-DDE, and mixture of OCPs were significantly associated with higher odds of infertility. The results suggest that exposure to chemicals may reduce the size of ovarian reserve in humans, and strongly encourage to study mechanisms behind POP-associated infertility in women in more detail.
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http://dx.doi.org/10.1016/j.envint.2021.106589DOI Listing
May 2021

Celebrating 100 years of AOGS with a focus on global health.

Acta Obstet Gynecol Scand 2021 04;100(4):561-563

Department of Clinical Research, University of Southern Denmark, Odense, Denmark.

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http://dx.doi.org/10.1111/aogs.14133DOI Listing
April 2021

Abortion-related near-miss morbidity and mortality in 43 health facilities with differences in readiness to provide abortion care in Uganda.

BMJ Glob Health 2021 Feb;6(2)

Public Health Sciences, Karolinska Institute, Stockholm, Sweden.

Introduction: With a view to inform policy for improved postabortion care, we describe abortion-related near-miss and mortality by sociodemographic risk factors and management options by pregnancy trimester in Uganda.

Methods: This secondary data analysis used an adapted WHO near-miss methodology to collect cross-sectional maternal near-miss and abortion complications data at 43 health facilities in Central and Eastern Uganda in 2016-2017. We computed abortion severe morbidity, near-miss and mortality ratios per 100 000 live births, and described the proportion of cases that worsened to an abortion near-miss or death, stratified by geographical region and trimester. We tested for association between independent variables and abortion near-miss, and obtained prevalence ratios for association between second trimester near-miss and independent demographic and management indicators. We assessed health facility readiness for postabortion care provision in Central and Eastern regions.

Results: Of 3315 recorded severe abortion morbidity cases, 1507 were near-misses. Severe abortion morbidity, near-miss and mortality ratios were 2063, 938 and 23 per 100 000 live births, respectively. Abortion-related mortality ratios were 11 and 57 per 100 000 in Central and Eastern regions, respectively. Abortion near-miss cases were significantly associated with referral (p<0.001). Second trimester had greater abortion mortality than first trimester. Eastern region had greater abortion-related morbidity and mortality than Central region with facilities in the former characterised by inferior readiness to provide postabortion care.

Conclusions: Uganda has a major abortion near-miss morbidity and mortality; with mortality higher in the second trimester. Life-saving commodities are lacking especially in Eastern region compromising facility readiness for postabortion care provision.
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http://dx.doi.org/10.1136/bmjgh-2020-003274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871269PMC
February 2021

Thirty years of mirena: A story of innovation and change in women's healthcare.

Acta Obstet Gynecol Scand 2021 04 23;100(4):614-618. Epub 2021 Feb 23.

Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Since its introduction in 1990, the levonorgestrel-releasing intrauterine system (LNG-IUS) has played a key role in shaping the healthcare landscape of women. Here we explore the development of the first LNG-IUS (Mirena®) and the early clinical trials that demonstrated its potential. We highlight the contraceptive and therapeutic benefits of Mirena®, and discuss how clinical practice has been changed since the introduction of LNG-IUS and other long-acting reversible contraceptive methods. The history of Mirena® is rich in innovation and has also paved the way to the development of smaller intrauterine systems with lower hormone doses. Along with Mirena®, these newer LNG-IUS contribute to improving contraceptive choices for women, allowing them to select the option that is right for them and that meets their needs no matter their age, parity or circumstances.
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http://dx.doi.org/10.1111/aogs.14110DOI Listing
April 2021

Natural Cycles app: contraceptive outcomes and demographic analysis of UK users.

Eur J Contracept Reprod Health Care 2021 Apr 4;26(2):105-110. Epub 2021 Feb 4.

Natural Cycles Nordic AB, Stockholm, Sweden.

Purpose: Digital fertility awareness-based contraception offers an alternative choice for women who do not wish to use hormonal or invasive methods. The aim of this study was to investigate the key demographics of current users of the Natural Cycles app and assess the contraceptive outcomes of women preventing pregnancy in a UK cohort of women.

Materials And Methods: This was a real world observational prospective observational study. The typical-use effectiveness of the method was calculated using both 13-cycle cumulative probability of pregnancy (life table analysis) and Pearl Index for the entire study cohort. Perfect-use PI was calculated using data from cycles where sexual intercourse during the fertile window was marked as protected and no unprotected sex was recorded on fertile days.

Results: 12,247 women were included in the study and contributed an average of 9.9 months of data for a total of 10,066 woman years of exposure. The mean age of the cohort was 30, mean BMI 23.4, the majority were in a stable relationship (83.2%) and had a university degree or higher (83%). The one year typical use, PI was 6.1 (95% CI: 5.6, 6.6) and with perfect-use was 2.0 (95% CI: 1.3, 2.8). 13 cycle pregnancy probability was 7.1%.

Conclusions: This is the first study which describes the use of a digital contraceptive by women in the UK. It describes the demographics of users and how they correlate with the apps effectiveness at preventing pregnancy.
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http://dx.doi.org/10.1080/13625187.2020.1867844DOI Listing
April 2021

More than just contraception: the impact of the levonorgestrel-releasing intrauterine system on public health over 30 years.

BMJ Sex Reprod Health 2021 Jan 29. Epub 2021 Jan 29.

Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Universal access to sexual and reproductive health services is essential to facilitate the empowerment of women and achievement of gender equality. Increasing access to modern methods of contraception can reduce the incidence of unplanned pregnancy and decrease maternal mortality. Long-acting reversible contraceptives (LARCs) offer high contraceptive efficacy as well as cost-efficacy, providing benefits for both women and healthcare systems. The levonorgestrel-releasing intrauterine system (LNG-IUS) first became available in 1990 with the introduction of Mirena (LNG-IUS 20), a highly effective contraceptive which can reduce menstrual blood loss and provide other therapeutic benefits. The impact of the LNG-IUS on society has been wide ranging, including decreasing the need for abortion, reducing the number of surgical sterilisation procedures performed, as well as reducing the number of hysterectomies carried out for issues such as heavy menstrual bleeding (HMB). In the context of the COVID-19 pandemic, Mirena can provide a treatment option for women with gynaecological issues such as HMB without organic pathology, minimising exposure to the hospital environment and reducing waiting times for surgical appointments. Looking to the future, research and development in the field of the LNG-IUS continues to expand our understanding of these contraceptives in clinical practice and offers the potential to further expand the choices available to women, allowing them to select the option that best meets their needs.
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http://dx.doi.org/10.1136/bmjsrh-2020-200962DOI Listing
January 2021

Towards individualised contraceptive counselling: clinical and reproductive factors associated with self-reported hormonal contraceptive-induced adverse mood symptoms.

BMJ Sex Reprod Health 2021 Jan 15. Epub 2021 Jan 15.

Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.

Objective: The study aim was to establish which demographic, clinical, reproductive and psychiatric factors are associated with self-reported hormonal contraceptive (HC)-induced adverse mood symptoms.

Study Design: We compiled baseline data from two Swedish studies: one cross-sectional study on combined oral contraceptive (COC)-induced adverse mood symptoms (n=118) and one randomised controlled trial on adverse mood symptoms on COC (n=184). Both included women eligible for COC use, aged over 18 years. All women answered a questionnaire on HC use and associated mood problems. The Mini-International Neuropsychiatric Interview (M.I.N.I.) was used to capture mood and anxiety disorders. Women who acknowledged HC-induced adverse mood symptoms, ongoing or previously (n=145), were compared with women without any such experience (n=157).

Results: Compared with women without self-reported HC-induced adverse mood symptoms, women with these symptoms were younger at HC start (adjusted odds ratio (aOR) 0.83, 95% CI 0.72 to 0.95), had more often undergone induced abortion (OR 3.36, 95% CI 1.57 to 7.23), more often suffered from an ongoing minor depressive disorder (n=12 vs n=0) and had more often experienced any previous mental health problem (aOR 1.90, 95% CI 1.01 to 3.59).

Conclusions: In line with previous research, this study suggests that women with previous or ongoing mental health problems and women who are younger at HC start are more likely to experience HC-induced adverse mood symptoms. Former and current mental health should be addressed at contraceptive counselling, and ongoing mental health disorders should be adequately treated.

Implications: This study adds valuable knowledge for identification of women susceptible to HC-induced adverse mood symptoms. It should facilitate the assessment of whether or not a woman has an increased risk of such symptoms, and thus enable clinicians to adopt a more personalised approach to contraceptive counselling.
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http://dx.doi.org/10.1136/bmjsrh-2020-200658DOI Listing
January 2021

A qualitative study on health care providers' experiences of providing comprehensive abortion care in Cox's Bazar, Bangladesh.

Confl Health 2021 Jan 13;15(1). Epub 2021 Jan 13.

Department of Women's and Children's Health, Karolinska Institutet, Widerströmska Huset, Floor 8, Tomtebodavägen 18A, SE-171 77, Stockholm, Sweden.

Background: Humanitarian settings are characterised by limited access to comprehensive abortion care. At the same time, humanitarian settings can increase the vulnerability of women and girls to unintended pregnancies and unsafe abortions. Humanitarian actors and health care providers can play important roles in ensuring the availability and accessibility of abortion-related care. This study explores health care providers' perceptions and experiences of providing comprehensive abortion care in a humanitarian setting in Cox's Bazar, Bangladesh and identifies barriers and facilitators in service provision.

Method: In-depth interviews (n = 24) were conducted with health care providers (n = 19) providing comprehensive abortion care to Rohingya refugee women and with key informants (n = 5), who were employed by an organisation involved in the humanitarian response. Data were analysed using an inductive content analysis approach.

Results: The national menstrual regulation policy provided a favourable legal environment and facilitated the provision of comprehensive abortion care, while the Mexico City policy created organisational barriers since it made organisations unable or unwilling to provide the full comprehensive abortion care package. Supplies were available, but a lack of space created a barrier to service provision. Although training from organisations had made the health care providers confident and competent and had facilitated the provision of services, their knowledge of the national abortion law and menstrual regulation policy was limited and created a barrier to comprehensive abortion services. Even though the health care providers were willing to provide comprehensive abortion care and had acquired skills and applied strategies to communicate with and provide care to Rohingya women, their personal beliefs and their perceptions of Rohingya women influenced their provision of care.

Conclusion: The availability and accessibility of comprehensive abortion care was limited by unfavourable abortion policies, a lack of privacy, a lack of knowledge of abortion laws and policies, health care providers' personal beliefs and a lack of cultural safety. To ensure the accessibility and availability of quality services, a comprehensive approach to sexual and reproductive health and rights is needed. Organisations must ensure that health care providers have knowledge of abortion policies and the ability to provide quality care that is woman-centred and non-judgmental.
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http://dx.doi.org/10.1186/s13031-021-00338-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805103PMC
January 2021

Contraceptive Effectiveness of an FDA-Cleared Birth Control App: Results from the Natural Cycles U.S. Cohort.

J Womens Health (Larchmt) 2021 Jun 23;30(6):782-788. Epub 2020 Dec 23.

Natural Cycles USA Corp, New York, New York, USA.

Digital fertility awareness-based methods of birth control are an attractive alternative to hormonal or invasive birth control for modern women. They are also popular among women who may be planning a pregnancy over the coming years and wish to learn about their individual menstrual cycle. The aim of this study was to assess the effectiveness of the Natural Cycles app at preventing pregnancy for a cohort of women from the United States and to describe the key demographics of current users of the app in such a cohort. This prospective real-world cohort study included users who purchased an annual subscription to prevent pregnancy. Demographics were assessed through answers to in-app questionnaires. Birth control effectiveness estimates for the entire cohort were calculated using 1-year pearl index (PI) and 13-cycle cumulative pregnancy probability (Kaplan-Meier life table analysis). The study included 5879 women who contributed an average of 10.5 months of data for a total of 5125 woman-years of exposure. The average user was 30 years old with a body mass index of 24 and reported being in a stable relationship. With typical use, the app had a 13-cycle cumulative pregnancy probability of 7.2% and a 1-year typical use PI of 6.2. When the app was used under perfect use, the PI was 2.0. The data presented in this study give insights into the cohort of women using this app in the United States, and provide country-specific effectiveness estimates. The contraceptive effectiveness of the app was in line with previously published figures from Natural Cycles (PI of seven for typical use and two for perfect use).
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http://dx.doi.org/10.1089/jwh.2020.8547DOI Listing
June 2021

A Review of Clinical Guidelines on the Management of Iron Deficiency and Iron-Deficiency Anemia in Women with Heavy Menstrual Bleeding.

Adv Ther 2021 01 27;38(1):201-225. Epub 2020 Nov 27.

Department of Women's and Children's Health, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden.

Introduction: Up to one-third of women of reproductive age experience heavy menstrual bleeding (HMB). HMB can give rise to iron deficiency (ID) and, in severe cases, iron-deficiency anemia (IDA).

Aim: To review current guidelines for the management of HMB, with regards to screening for anemia, measuring iron levels, and treating ID/IDA with iron replacement therapy and non-iron-based treatments.

Methods: The literature was searched for English-language guidelines relating to HMB published between 2010 and 2020, using the PubMed database, web searching, and retrieval of clinical guidelines from professional societies.

Results: Overall, 55 guidelines mostly originating from North America and Europe were identified and screened. Twenty-two were included in this review, with the majority (16/22) focusing on guidance to screen women with HMB for anemia. The guidance varied with respect to identifying symptoms, the criteria for testing, and diagnostic hemoglobin levels for ID/IDA. There was inconsistency concerning screening for ID, with 11/22 guidelines providing no recommendations for measurement of iron levels and four contrasting guidelines explicitly advising against initial assessment of iron levels. In terms of treatment, 8/22 guidelines provided guidance on iron therapy, with oral iron administration generally recommended as first-line treatment for ID and/or IDA. Four guidelines recommended intravenous iron administration for severe anemia, in non-responders, or before surgery. Three guidelines provided hemoglobin thresholds for choosing between oral or intravenous iron treatment. Four guidelines discussed the use of transfusion for severe IDA.

Conclusion: Many of the guidelines for managing HMB recognize the importance of treating anemia, but there is a lack of consensus in relation to screening for ID and use of iron therapy. Consequently, ID/IDA associated with HMB is likely to be underdiagnosed and undertreated. A consensus guidance, covering all aspects of screening and management of ID/IDA in women with HMB, is needed to optimize health outcomes in these patients.
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http://dx.doi.org/10.1007/s12325-020-01564-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695235PMC
January 2021

How task-sharing in abortion care became the norm in Sweden: A case study of historic and current determinants and events.

Int J Gynaecol Obstet 2020 Jul;150 Suppl 1:34-42

Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.

We performed a country case study using thematic analysis of interviews and existing grey and published literature to identify facilitators and barriers to the implementation of midwife-provided abortion care in Sweden. Identified facilitating factors were: (1) the historical role and high status of Swedish midwives; (2) Swedish research and development of medical abortion that enabled an enlarged clinical role for midwives; (3) collaborations between individual clinicians and researchers within the professional associations, and the autonomy of clinical units to implement changes in clinical practice; (4) a historic precedent of changes in abortion policy occurring without prior official or legal sanction; (5) a context of liberal abortion laws, secularity, gender equality, public support for abortion, trust in public institutions; and (6) an increasing global interest in task-shifting to increase access and reduce costs. Identified barriers/risks were: (1) the lack of systems for monitoring and evaluation; and (2) a loss of physician competence in abortion care.
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http://dx.doi.org/10.1002/ijgo.13003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539959PMC
July 2020

How the coronavirus disease 2019 pandemic is impacting sexual and reproductive health and rights and response: Results from a global survey of providers, researchers, and policy-makers.

Acta Obstet Gynecol Scand 2021 04 3;100(4):571-578. Epub 2020 Dec 3.

Department of Women and Children's Health, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden.

Introduction: We aimed to give a global overview of trends in access to sexual and reproductive health and rights (SRHR) during the coronavirus disease 2019 (COVID-19) pandemic and what is being done to mitigate its impact.

Material And Methods: We performed a descriptive analysis and content analysis based on an online survey among clinicians, researchers, and organizations. Our data were extracted from multiple-choice questions on access to SRHR services and risk of SRHR violations, and written responses to open-ended questions on threats to access and required response.

Results: The survey was answered by 51 people representing 29 countries. Eighty-six percent reported that access to contraceptive services was less or much less because of COVID-19, corresponding figures for surgical and medical abortion were 62% and 46%. The increased risk of gender-based and sexual violence was assessed as moderate or severe by 79%. Among countries with mildly restrictive abortion policies, 69% had implemented changes to facilitate access to abortion during the pandemic, compared with none among countries with severe restrictions (P < .001), 87.5% compared with 46% had implemented changes to facilitate access to contraception (P = .023). The content analysis showed that (a) prioritizations in health service delivery at the expense of SRHR, (b) lack of political will, (c) the detrimental effect of lockdown, and (d) the suspension of sexual education, were threats to SRHR access (theme 1). Requirements to mitigate these threats (theme 2) were (a) political will and support of universal access to SRH services, (b) the sensitization of providers, (c) free public transport, and (d) physical protective equipment. A contrasting third theme was the state of exception of the COVID-19 pandemic as a window of opportunity to push forward women's health and rights.

Conclusions: Many countries have seen decreased access to and increased violations of SRHR during the COVID-19 pandemic. Countries with severe restrictions on abortion seem less likely to have implemented changes to SRHR delivery to mitigate this impact. Political will to support the advancement of SRHR is often lacking, which is fundamental to ensuring both continued access and, in a minority of cases, the solidification of gains made to SRHR during the pandemic.
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http://dx.doi.org/10.1111/aogs.14043DOI Listing
April 2021

Abortion regulation in Europe in the era of COVID-19: a spectrum of policy responses.

BMJ Sex Reprod Health 2020 Oct 22. Epub 2020 Oct 22.

Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.

Background: Unprecedented public health actions restricting movement and non-COVID related health services are likely to have affected abortion care during the pandemic in Europe. In the absence of a common approach to ensure access to this essential health service, we sought to describe the variability of abortion policies during the outbreak in Europe in order to identify strategies that improve availability and access to abortion in times of public health crises.

Methods: We collected information from 46 countries/regions: 31 for which country-experts completed a survey and 15 for which we conducted a desk review. We describe abortion regulations and changes to regulations and practice during the pandemic.

Results: During COVID-19, abortions were banned in six countries and suspended in one. Surgical abortion was less available due to COVID-19 in 12 countries/regions and services were not available or delayed for women with COVID-19 symptoms in eleven. No country expanded its gestational limit for abortion. Changes during COVID-19, mostly designed to reduce in-person consultations, occurred in 13 countries/regions. Altogether eight countries/regions provided home medical abortion with mifepristone and misoprostol beyond 9 weeks (from 9 weeks+6 days to 11 weeks+6 days) and 13 countries/regions up to 9 weeks (in some instances only misoprostol could be taken at home). Only six countries/regions offered abortion by telemedicine.

Conclusions: The lack of a unified policy response to COVID-19 restrictions has widened inequities in abortion access in Europe, but some innovations including telemedicine deployed during the outbreak could serve as a catalyst to ensure continuity and equity of abortion care.
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http://dx.doi.org/10.1136/bmjsrh-2020-200724DOI Listing
October 2020

Natural killer cells and type II interferon in Ro/SSA and La/SSB autoantibody-exposed newborns at risk of congenital heart block.

Ann Rheum Dis 2021 02 1;80(2):194-202. Epub 2020 Oct 1.

Division of Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

Objective: Congenital heart block (CHB) with immune cell infiltration develops in the fetus after exposure to maternal Ro/La autoantibodies. CHB-related serology has been extensively studied, but reports on immune-cell profiles of anti-Ro/La-exposed neonates are lacking. In the current study, we characterised circulating immune-cell populations in anti-Ro/La+mothers and newborns, and explored potential downstream effects of skewed neonatal cell populations.

Methods: In total, blood from mothers (n=43) and neonates (n=66) was sampled at birth from anti-Ro/La+ (n=36) and control (n=30) pregnancies with or without rheumatic disease and CHB. Flow cytometry, microarrays and ELISA were used for characterising cells and plasma.

Results: Similar to non-pregnant systemic lupus erythematosus and Sjögren-patients, anti-Ro/La+mothers had altered B-cell subset frequencies, relative T-cell lymphopenia and lower natural killer (NK)-cell frequencies. Surprisingly, their anti-Ro/La exposed neonates presented higher frequencies of CD56CD16 NK cells (p<0.01), but no other cell frequency differences compared with controls. Type I and II interferon (IFN) gene-signatures were revealed in neonates of anti-Ro/La+ pregnancy, and exposure of fetal cardiomyocytes to type I IFN induced upregulation of several NK-cell chemoattractants and activating ligands. Intracellular flow cytometry revealed IFNγ production by NK cells, CD8 and CD4 T cells in anti-Ro/La exposed neonates. IFNγ was also detectable in their plasma.

Conclusion: Our study demonstrates an increased frequency of NK cells in anti-Ro/La exposed neonates, footprints of type I and II IFN and an upregulation of ligands activating NK cells in fetal cardiac cells after type I IFN exposure. These novel observations demonstrate innate immune activation in neonates of anti-Ro/La+pregnancy, which could contribute to the risk of CHB.
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http://dx.doi.org/10.1136/annrheumdis-2019-216786DOI Listing
February 2021

Vaginal bromocriptine for treatment of adenomyosis: Impact on magnetic resonance imaging and transvaginal ultrasound.

Eur J Obstet Gynecol Reprod Biol 2020 Nov 24;254:38-43. Epub 2020 Aug 24.

Department of Women´s and Children´s Health, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden.

Objective: Vaginal bromocriptine significantly reduces heavy menstrual bleeding and pain in women with diffuse adenomyosis. The aim of this pilot study was to evaluate whether imaging findings of adenomyosis, as assessed by transvaginal ultrasound (TVU) and magnetic resonance imaging (MRI) reflect changes induced by the bromocriptine treatment.

Study Design: Eighteen women, aged 35-50, with heavy menstrual bleeding reporting Pictorial Blood Loss Assessment Chart (PBLAC) scores >100 and diffuse adenomyosis according to both MRI and TVU were included. The subjects underwent treatment with vaginal bromocriptine for 6 months. MRI and TVU were performed at baseline and after 6 months of medication.

Results: Mean age of the participants was 44.8 years, 77.8 % reported PBLAC scores > 250 and 66.7 % reported moderate to severe pain during menstruation at baseline. As compared to baseline, TVU revealed a thinner maximal Junctional Zone (JZmax) (8.5 mm [5.2-14] vs 7.9 mm [5-11.2], p = 0.02) at 6 months. Asymmetric wall thickening was seen in 13 (72 %) at baseline, and in 6 (33 %) women at 6 months, p = 0.02. No significant changes were seen in irregular endometrial-myometrial border, presence of fan-shaped shadowing, cystic changes, striations, hyperechogenic islands or lesion extension. MRI showed no significant difference in JZmax (16.0 mm[12.1-27.7] vs 15.5 mm [9.5-25.8], p = 0.81), JZdifference (9.5 mm[4.8-21.6] vs 8.4[3.8-19.5], p = 1) or Ratio JZ/myometrium (0.6 [0.5-0.8] vs. 0.6[0.4-0.8], p = 0.9) at baseline vs 6 month. Cystic lesions in the JZ were found in 9 women (50 %) before, and in 5 women (28 %) at 6 months, p = 0.13.

Conclusion: TVU showed a significant decrease in JZ max and a reduced number of women with asymmetric myometrial wall thickness. The changes seen in this small pilot study may indicate that vaginal bromocriptine have an impact on adenomyosis that is reflected in radiological appearance.
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http://dx.doi.org/10.1016/j.ejogrb.2020.08.040DOI Listing
November 2020

Syndecan-1 modulates the invasive potential of endometrioma via TGF-β signalling in a subgroup of women with endometriosis.

Hum Reprod 2020 10;35(10):2280-2293

Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, S-171 76 Stockholm, Sweden.

Study Question: What is the physiological role of transforming growth factor-beta (TGF-β1) and syndecans (SDC1, SDC4) in endometriotic cells in women with endometriosis?

Summary Answer: We observed an abnormal, pro-invasive phenotype in a subgroup of samples with ovarian endometriosis, which was reversed by combining gene silencing of SDC1 with the TGF-β1 treatment.

What Is Known Already: Women with endometriosis express high levels of TGF-β1 and the proteoglycan co-receptors SDC1 and SDC4 within endometriotic cysts. However, how SDC1 and SDC4 expression is regulated by TGF-β1 and the physiological significance of the high expression in endometriotic cysts remains unknown as does the potential role in disease severity.

Study Design, Size, Duration: We utilized a pre-validated panel of stem- and cancer cell-associated markers on endometriotic tissue (n = 15) to stratify subgroups of women with endometriosis. Furthermore, CD90+CD73+CD105+ (SC+) endometriotic stromal cells from these patient subgroups were explored for their invasive behaviour in vitro by transient gene inhibition of SDC1 or SDC4, both in the presence or absence of TGF-β1 treatment.

Participants/materials, Setting, Methods: Endometriotic cyst biopsies (n = 15) were obtained from women diagnosed with ovarian endometriosis (ASRM Stage III-IV). Gene expression variability was assessed on tissue samples by applying gene clustering tools for the dataset generated from the pre-validated panel of markers. Three-dimensional (3D) spheroids from endometriotic SC+ were treated in vitro with increasing doses of TGF-β1 or the TGFBRI/II inhibitor Ly2109761 and assessed for SDC1, SDC4 expression and in vitro 3D-spheroid invasion. Transcriptomic signatures from the invaded 3D spheroids were evaluated upon combining transient gene silencing of SDC1 or SDC4, both in presence or absence of TGF-β1 treatment. Furthermore, nanoscale changes on the surface of endometriotic cells were analysed after treatment with TGF-β1 or TGFBRI/II inhibitor using atomic force microscopy.

Main Results And The Role Of Chance: Gene clustering analysis revealed that endometriotic tissues displayed variability in their gene expression patterns; a small subgroup of samples (2/15, Endo-hi) exhibited high levels of SDC1, SDC4 and molecules involved in TGF-β signalling (TGF-β1, ESR1, CTNNB1, SNAI1, BMI1). The remaining endometriotic samples (Endo-lo) showed a uniform, low gene expression profile. Three-dimensional spheroids derived from Endo-hi SC+ but not Endo-lo SC+ samples showed an aberrant expression of SDC1 and exhibited enhanced 3D-spheroid invasion in vitro, upon rhTGF-β1 treatment. However, this abnormal, pro-invasive response of Endo-hi SC+ was reversed upon gene silencing of SDC1 with the TGF-β1 treatment. Interestingly, transcriptomic signatures of 3D spheroids silenced for SDC1 and consecutively treated with TGF-β1, showed a down-regulation of cancer-associated pathways such as WNT and GPCR signalling.

Large Scale Data: Transcriptomic data were deposited in NCBI's Gene Expression Omnibus (GEO) and could be retrieved using GEO series accession number: GSE135122.

Limitations, Reasons For Caution: It is estimated that about 2.5% of endometriosis patients have a potential risk for developing ovarian cancer later in life. It is possible that the pro-oncogenic molecular changes observed in this cohort of endometriotic samples may not correlate with clinical occurrence of ovarian cancer later in life, thus a validation will be required.

Wider Implications Of The Findings: This study emphasizes the importance of interactions between syndecans and TGF-β1 in the pathophysiology of endometriosis. We believe that this knowledge could be important in order to better understand endometriosis-associated complications such as ovarian cancer or infertility.

Study Funding/competing Interest(s): This study was funded by Cancerfonden (CAN 2016/696), Radiumhemmets Forskningsfonder (Project no. 154143 and 184033), EU MSCA-RISE-2015 project MOMENDO (691058), Estonian Ministry of Education and Research (IUT34-16), Enterprise Estonia (EU48695) and Karolinska Institute. Authors do not have any conflict of interest.
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http://dx.doi.org/10.1093/humrep/deaa164DOI Listing
October 2020

Repeat testing without having 'the talk' is not meaningful'-healthcare providers' perceptions on finding a balance between testing and primary prevention strategies. A qualitative study in Stockholm, Sweden.

BMJ Open 2020 08 5;10(8):e034179. Epub 2020 Aug 5.

Global Public Health, Karolinska Institutet, Stockholm, Sweden.

Objectives: is a public health problem. Widespread testing and re-testing after a sexually transmitted infection (STI) is recommended to contain the epidemic and has been adopted by many countries. A recent study in Stockholm found that serial testing was used as a substitute for condom use by youth presenting at the Youth Health Clinics (YHC). The objectives of this study are to explore frontline healthcare provider's perception of youth testing repeatedly for as a substitute for condom use and their views on how this might be addressed.

Design: Qualitative study, in-depth interviews and analysed using content analysis.

Setting: YHC in Stockholm County, Sweden.

Participants: Healthcare providers (HCPs) working at the YHC.

Findings: Testing used as a method of prevention of STIs by youth has been a well-known phenomenon observed by HCPs at the YHC. Despite frustration regarding this behaviour, attitudes towards youth visiting the clinics repeatedly were overall positive. It is seen as an opportunity to reach youth with primary prevention strategies. Time for in-depth conversations with the youth is considered essential to understand the various reasons behind sexual risk-taking and to tailor counselling accordingly. Introducing concepts of self-compassion and self-respect in relation to sex is thought of as an effective intervention to improve sexual health among youth.

Conclusion: HCPs' views on testing repeatedly for as means of prevention, range widely from seeing this as 'a positive strategy for prevention' to 'a waste of healthcare resources'. There was a more unified view on how this should be addressed. Testing without having time to problematise sexual risk-taking was seen as meaningless. In depth, one-on-one counselling was deemed important. While scaling up accessibility to testing services, primary prevention strategies must not be neglected.
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http://dx.doi.org/10.1136/bmjopen-2019-034179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409961PMC
August 2020

Hand-held device to remove a single-rod subdermal contraceptive implant: Results of early trials in Sweden.

Contraception 2020 12 18;102(6):424-427. Epub 2020 Jul 18.

Department of Women's and Children's Health, Karolinska Institutet, WHO-centre, QB:84, Karolinska vägen 37 A, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. Electronic address:

Objective: Long-acting reversible contraceptives (LARCs) such as subdermal implants and intrauterine devices are promoted and increasingly used worldwide. Hence, in the light of this we also need to ensure easy access to the reversibility, i.e. emphasise the R in LARC. Our overall aim is to develop a device to facilitate implant removals. We evaluated the safety and performance of the two initial field prototypes where the main outcome was percentage of successful fixations and secondary outcomes were percentage of successful removals without the use of additional tools, duration of the procedure, satisfaction and adverse events.

Study Design: We performed a feasibility study including 41 subjects.

Results: We estimated a fixation rate of 35/41 (85%) and an overall removal rate of 24/41 (59%). Further, we measured that the median time for removals was 80 s and that subjects and operators were satisfied with the procedure. We recorded adverse events such as bruising and superficial abrasions.

Conclusions: The device demonstrated a successful fixation rate, however, the removal rate will need to be further improved.

Implications: This feasibility study shows that the device has potential and further research is needed to modify and optimize the device.
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http://dx.doi.org/10.1016/j.contraception.2020.07.005DOI Listing
December 2020

Effects of the levonorgestrel intrauterine system on the endometrium after long-term exposure to mifepristone: Secondary outcomes of a randomized controlled trial.

Eur J Obstet Gynecol Reprod Biol 2020 Sep 26;252:330-335. Epub 2020 Jun 26.

Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.

Objective: Long-term treatment with progesterone receptor modulators (PRM) is associated with a distinct histological entity termed progesterone receptor modulator associated endometrial changes (PAEC). While accumulating evidence implies that these changes are benign and reversible after cessation of treatment, there are currently no data underpinning their development. Consequently, as a precaution, endometrial shedding is recommended after long-term PRM intake. Avoiding endometrial shedding after treatment with a PRM and prior to the start of a progestin treatment would be beneficial for women in reproductive age to avoid pregnancy and bleeding. However, the endometrial morphology with such a treatment regimen is unknown. The aim of this study was to delineate the endometrial morphology following continuous long-term treatment with the PRM mifepristone and subsequent placement of a levonorgestrel intrauterine system (LNG-IUS) without prior shedding of the endometrium.

Study Design: This study reports the secondary outcome from a double-blinded randomized controlled trial conducted at Karolinska University Hospital, Sweden, November 2009 to January 2015. Healthy women aged 18-43 years with regular menstrual cycles were included. Eligible women were randomized to receive either 50 mg of mifepristone (n = 29) or a comparator (n = 29), every other day for two months followed by insertion of an LNG-IUS 52 mg. Endometrial biopsies were obtained at baseline and three months after placement of the device. The samples were histologically assessed. The main outcome measure of this sub-study was the endometrial morphology including presence of PAEC three months after LNG-IUS insertion.

Results: Nine and eight paired biopsies from the mifepristone and comparator group, respectively, were included in the histological analysis. There were no differences in baseline characteristics between the groups and all baseline endometrial biopsies were physiological. Three months after LNG-IUS placement the endometrial morphology was still benign without PAEC in all samples treated with either mifepristone or comparator. A progestin effect on the endometrium was seen in all samples.

Conclusions: Placement of an LNG-IUS immediately following two months' treatment with the PRM mifepristone, without any prior shedding of the endometrium, may represent a feasible approach in terms of endometrial safety. However, larger studies are needed to confirm our results.
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http://dx.doi.org/10.1016/j.ejogrb.2020.06.056DOI Listing
September 2020

Information on early medical abortion for women using an audiovisual animation vs face-to-face consultation: A consortium randomized and quasi-randomized trial.

Acta Obstet Gynecol Scand 2020 12 12;99(12):1611-1617. Epub 2020 Jul 12.

MRC Center for Reproductive Healthcare, University of Edinburgh, Edinburgh, UK.

Introduction: There is some evidence that audiovisual formats can be an effective way of providing information about early medical abortion (EMA). A short animation (3 minutes) was developed about EMA in three languages that summarized the EMA process for use in the UK, France and Sweden.

Material And Methods: We conducted a multicenter randomized controlled trial to compare information on EMA delivered by an animated film vs a face-to-face consultation. Women requesting EMA (≤9 weeks' gestation) from abortion clinics in Edinburgh (UK), Paris (France) and Stockholm (Sweden) were recruited. The primary outcome was women's recall of prespecified key information on EMA. Secondary outcomes were acceptability of mode of information delivery, clarity and helpfulness of information rated on a Likert scale. The study was prospectively registered with clinicaltrials.gov, ID number: NCT03417362.

Results: 172 women completed the study (Edinburgh = 50, Paris = 78, Stockholm = 48). There was no statistically significant difference in recall scores between the animation and standard arms in Edinburgh and Stockholm sites. However, the difference between arms at the Paris site was statistically significant (P = .007) in favor of the animation. All participants in the animation arm rated it as an acceptable way to receive information on EMA.

Conclusions: A "short" audiovisual animation can adequately and acceptably deliver key information about EMA. This intervention could be used routinely to provide standardized and high-quality information to women seeking EMA.
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http://dx.doi.org/10.1111/aogs.13944DOI Listing
December 2020

Efficacy and safety of vilaprisan in women with uterine fibroids: Data from the phase 2b randomized controlled trial ASTEROID 2.

Eur J Obstet Gynecol Reprod Biol 2020 Sep 31;252:7-14. Epub 2020 May 31.

Bayer AG, Müllerstraße 178, 13342, Berlin, Germany. Electronic address:

Objective: To assess the efficacy of vilaprisan compared with placebo in the management of the symptoms of uterine fibroids (UF), with a secondary objective to provide a descriptive comparison with ulipristal acetate.

Study Design: The randomized, parallel-group, double-blind, placebo- and active-controlled, multicenter ASTEROID 2 trial assessed the efficacy and safety of vilaprisan versus placebo and ulipristal acetate for two 12-week treatment periods in women with ≥1 UF experiencing heavy menstrual bleeding (HMB). The primary endpoint compared the efficacy of vilaprisan with placebo at 12 weeks, assessed as the absence of bleeding/spotting by bleeding diary. Secondary endpoints compared the efficacy of vilaprisan with ulipristal acetate. Results of the first 12-week treatment period are reported here.

Results: Women (mean age 42.5 years) were enrolled from 1 June 2015. At baseline, mean menstrual blood loss per 28 days was 214.1 mL and the volume of the three largest UF was 106.2 mL. In total, 155 women completed the initial 12-week treatment period. Complete absence of bleeding/spotting until the end of the 12-week treatment period was achieved by 62.9 % of women receiving vilaprisan versus 0.0 % with placebo (p < .001); 55.4 % of women treated with ulipristal acetate reported absence of bleeding/spotting. The predefined HMB response (<80 mL and >50 % reduction from baseline during the last 28 days of treatment) was observed in 95.7 % of subjects treated with vilaprisan and 86.5 % of subjects treated with ulipristal acetate. Vilaprisan and ulipristal acetate treatment reduced the sum of the volume of the three largest UF by 29.9 % and 23.8 %, respectively, whereas an increase of 6.3 % was observed in the placebo group. No safety concerns, including multiple laboratory parameters, were identified.

Conclusion: Daily administration of vilaprisan 2 mg induced amenorrhea, controlled bleeding, decreased UF size, and was well tolerated in women with HMB associated with UF.

Clinical Trial Registration: ClinicalTrials.gov number: NCT02465814 https://clinicaltrials.gov/ct2/show/NCT02465814.
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http://dx.doi.org/10.1016/j.ejogrb.2020.05.043DOI Listing
September 2020

Modern contraceptive use among female refugee adolescents in northern Uganda: prevalence and associated factors.

Reprod Health 2020 May 20;17(1):67. Epub 2020 May 20.

Department of Obstetrics and Gynaecology, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda.

Background: Adolescent pregnancies are persistently high among refugees. The pregnancies have been attributed to low contraceptive use in this population. The aim of this study was to determine the prevalence and factors associated with modern contraceptive use among female refugee adolescents in northern Uganda.

Methods: This was a cross sectional study using both descriptive and analytical techniques. The study was carried out in Palabek refugee settlement in Northern Uganda from May to July 2019. A total of 839 refugee adolescents who were sexually active or in-union were consecutively enrolled. Interviewer administered questionnaires were used for data collection.

Results: Modern contraceptive prevalence was 8.7% (95% CI: 7.0 to 10.8). The injectable was the most commonly used modern contraceptive method [42.5% (95% CI: 31.5 to 54.3)], and most of the participants had used the contraceptives for 6 months or less (59.7%). Reasons for not using modern contraceptives included fear of side effects (39.3%), partner prohibition (16.4%), and the desire to become pregnant (7.0%). Participants who were married (OR = 0.11, 95% CI: 0.04 to 0.35, p < 0.001), cohabiting (OR = 0.43, 95% CI: 0.20 to 0.93, p = 0.032) or having an older partner (OR = 0.93, 95% CI: 0.86 to 0.99, p = 0.046) were less likely to use modern contraceptives.

Conclusion: Modern contraceptive use among female refugee adolescents was very low, and few reported a desire to become pregnant, leaving them vulnerable to unplanned pregnancies. Least likely to use modern contraceptives were participants who were married/cohabiting and those having older partners implying a gender power imbalance in fertility decision making. There is an urgent need for innovations to address the gender and power imbalances within relationships, which could shape fertility decision-making and increase modern contraceptive use among refugee adolescents.
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http://dx.doi.org/10.1186/s12978-020-00921-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238518PMC
May 2020

Oestrogen-free oral contraception with a 4 mg drospirenone-only pill: new data and a review of the literature.

Eur J Contracept Reprod Health Care 2020 Jun 21;25(3):221-227. Epub 2020 Apr 21.

Clinic for Obstetrics and Gynecology, University Hospital Basel, Basel, Switzerland.

The contraceptive pill is an effective and safe method of preventing pregnancy. The progestins used for contraception either are components of a combined hormonal contraceptive (tablets, patches or vaginal rings) or are used alone in progestin-only formulations. Progestin-only contraceptives are available as daily oral preparations, subcutaneous or intramuscular injectables (every 1-3 months), subdermal implants (every 3-5 years) and intrauterine systems (every 3-5 years). Long-acting progestins are highly effective in typical use and have a very low risk profile and few contraindications. A new progestin-only, oestrogen-free contraceptive, drospirenone, in a dosage of 4 mg/day in a 24/4 regimen, has received regulatory approval in the USA and the EU. The molecule has antigonadotropic, antimineralocorticoid, antiestrogenic and antiandrogenic properties. The regimen was chosen to improve the bleeding profile; maintain plasma oestradiol levels at those of the early follicular phase, to avoid hypoestrogenism; and preserve efficacy even with a missed pill, as drospirenone has a half-life of 30-34 h. Clinical studies have shown good efficacy, very low cardiovascular side effects and a favourable bleeding pattern, as well as maintenance of ovulation inhibition after scheduled 24 h delays in pill intake.
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http://dx.doi.org/10.1080/13625187.2020.1743828DOI Listing
June 2020

Multicenter, open-label trial to assess the safety and tolerability of drospirenone 4.0 mg over 6 cycles in female adolescents, with a 7-cycle extension phase.

Contraception 2020 06 21;101(6):412-419. Epub 2020 Feb 21.

Praxis Dr. Peters, Berner Heerweg 157, 22159 Hamburg, Germany.

Objective: To assess the safety, tolerability and bleeding patterns of drospirenone 4.0 mg.

Study Design: A multicenter, open-label, safety trial in sexually-active adolescents aged 12-17 years for six 28-day treatment cycles (Core Phase) and an optional 7-13 cycle extension with administration of drospirenone 4.0 mg in a regimen of 24 active/4 placebo tablets.

Results: We enrolled 111 subjects, and after eight failed Screening and one withdrew consent, 102 remained evaluable; 89 (87.3%) completed the Core Phase. Overall, treatment with drospirenone 4.0 mg was well tolerated. Possibly-related TEAEs were reported for 23 subjects (22.5% of the 102 evaluable); two serious adverse events were reported during the Extension Phase (pharyngitis and joint dislocation), neither related to treatment. The number of subjects reporting dysmenorrhea decreased from 47 prior to Screening, to 14 at the end of Cycle 6, to 8 at the end of Cycle 13. Assessments of vital signs and gynecological and physical examinations were unremarkable. We observed a trend towards less bleeding and/or spotting over the first cycles with the use of drospirenone: the proportion of subjects with both scheduled and unscheduled bleeding and spotting decreased, while the proportion with absence of bleeding or spotting increased. Only five subjects (4.9% of 102 evaluable) prematurely terminated the trial due to irregular bleeding. At the end of 6 months, 85.3% rated the tolerability of drospirenone as "excellent" or "good".

Conclusions: The results indicate that 4.0 mg drospirenone over 13 treatment cycles was well tolerated, safe and acceptable for the majority of adolescents.

Implications: Drospirenone 4.0 mg oral pills provide a well-tolerated, safe and acceptable contraceptive choice for adolescents.
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http://dx.doi.org/10.1016/j.contraception.2020.02.004DOI Listing
June 2020

Risk factors for poor neonatal outcome in pregnancies with decreased fetal movements.

Acta Obstet Gynecol Scand 2020 08 12;99(8):1014-1021. Epub 2020 Mar 12.

Department of Clinical Science and Education, Karolinska Institutet, Soder Hospital, Stockholm, Sweden.

Introduction: The incidence of Swedish stillbirths has varied little in the past 40 years, with a reported frequency of 400-450 stillbirths/y (approximately 4‰), despite increased information about fetal movement in the media and awareness among healthcare providers. The objectives of this project were to describe the outcome of pregnancies with reduced fetal movement in a Swedish context and to investigate factors associated with poor neonatal outcome in this group.

Material And Methods: A retrospective cohort study was performed at Soder Hospital, Stockholm, Sweden. All single pregnancies at the hospital from January 2016 to December 2017 presenting with reduced fetal movement after 22 gestational weeks were included in the study. A composite neonatal outcome was constructed: 5-minute Apgar score ≤7, arterial pH in the umbilical cord ≤7.10, transfer to neonatal care unit for further care or intrauterine fetal death.

Results: For women seeking care for reduced fetal movement, the occurrence of composite poor neonatal outcome ranged from 6.2% to 18.4% within different groups. The highest risk for poor neonatal outcome (18.4%) was found in the group of women with a small-for-gestational-age fetus. Another high-risk group (12.8%) was the one comprising women with normal birthweight/large-for-gestational-age fetuses with an in vitro fertilization pregnancy.

Conclusions: The highest incidence of poor neonatal outcome among women with reduced fetal movement was found in the groups with small-for-gestational-age fetuses in nulliparous and multiparous women. A routine ultrasound assessment for fetal growth in third trimester is supposedly most efficient to identify undiagnosed small for gestational age.
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http://dx.doi.org/10.1111/aogs.13827DOI Listing
August 2020

Management of very early medical abortion-An international survey among providers.

Eur J Obstet Gynecol Reprod Biol 2020 Mar 1;246:169-176. Epub 2020 Feb 1.

Department of Women's and Children's Health, Division of Obstetrics and Gynaecology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.

Objective: To record the definition and management of Very Early Medical Abortion (VEMA) in different countries.

Study Design: An Internet survey was circulated internationally among providers of medical abortion via a website. The questionnaire focused on reasons for performing or delaying medical abortion at a very early gestational age and the perceived advantages and disadvantages of VEMA.

Results: Out of 220 completed questionnaires, 50 % came from European abortion providers (n = 110). Most respondents (72 %) defined VEMA as abortion performed in the presence of a positive hCG pregnancy test but with an empty uterine cavity or a gestational sac-like structure, and no signs or symptoms of ectopic pregnancy. A total of 74 % of respondents thought it was not necessary to wait for a diagnosis of intrauterine pregnancy before starting medical abortion. Equally, 74 % were aware of the possibility of an ectopic pregnancy.

Conclusion: According to European providers of medical abortion, waiting for the diagnosis of an intrauterine pregnancy is not necessary and does not improve treatment of ectopic pregnancy. Providers should know that medical abortion can be performed effectively and safely as soon as the woman has decided. There is no lower gestational age limit.
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http://dx.doi.org/10.1016/j.ejogrb.2020.01.022DOI Listing
March 2020

Sexual and reproductive health and rights of refugee and migrant women: gynecologists' and obstetricians' responsibilities.

Int J Gynaecol Obstet 2020 Apr 18;149(1):113-119. Epub 2020 Feb 18.

Department of Women's and Children's Health, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden.

Ensuring universal access to sexual and reproductive healthcare services is Target 3.7 of the United Nations Sustainable Development Goals (SDG). Refugee and migrant women and children are at particular risk of being forgotten in the global momentum to achieve this target. In this article we discuss the violations of sexual and reproductive health and rights (SRHR) of particular relevance to the refugee and migrant reality. We give context-specific examples of denial of health services to vulnerable groups; lack of dignity as a barrier to care; the vulnerability of adolescents; child marriage; weaponized rape; gender-based violence; and sexual trafficking. We discuss rights frameworks and models that are being used in response to these situations, as well as what remains to be done. Specifically, we call for obstetricians and gynecologists to act as individual providers and through their FIGO member societies to protect women's health and rights in these exposed settings.
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http://dx.doi.org/10.1002/ijgo.13111DOI Listing
April 2020